F. Project Summary: Project 2 Adipocytes are highly specialized cells that play a major role in energy homeostasis in vertebrates. One of the major changes that contribute to metabolic dysfunction in individuals exposed to an obesogenic environment is the inability to resist a gain in fat mass or to maintain adipocyte function. Adipocyte dysfunction can be caused by an inability to store free fatty acids and by alterations in secreted hormones like adiponectin, leading to global metabolic dysregulation. We have identified three botanicals (Artemisia scoparia, groundsel bush [Baccharis halimifolia], & fenugreek [Trigonella foenum graecum L.]) whose mechanisms lead to a common metabolic outcome. Specifically, each of these highly distinct botanicals increases adiponectin expression and secretion from adipocytes and there is evidence they can attenuate proinflammatory states. While each likely mediates its effects via different mechanisms and cellular pathways, the common result has important implications for pursuing the fundamental pathways and signals by which botanicals can increase adiponectin expression to mediate botano-metabolic resiliency. Many botanicals (i.e. raspberry, green tea) are widely marketed and promoted to combat obesity. Unfortunately, the claims made regarding these extracts and other botanicals are not supported by mechanistic studies or clinical trials. In contrast, our studies during the last funding cycle have provided considerable evidence demonstrating the potential of specific botanicals to modulate favorable metabolic effects on adipocyte development and function thus supporting our Center concept of ?botano-metabolic resiliency?. Our long term objective is use in vitro and in vivo approaches to identify active components and determine the mechanisms of action of select botanicals on adipocytes and how these contribute to whole body resiliency.